Abstract
Under appropriate culture conditions, ES cells will spontaneously differentiate and generate colonies known as embryoid bodies (EBs) that contain precursors of multiple lineages, including those of the hematopoietic system (1–7). Previous studies have demonstrated that the molecular events leading to hematopoietic commitment, as well as the kinetics of lineage development within the EBs, parallel that found in the normal mouse embryo (5). More recent studies (8–11) have supported these earlier findings and have provided evidence that hematopoietic development within EBs can be divided into the following distinct stages: hemangioblast, primitive and early definitive, and multilineage definitive. These stages most closely correspond to the preblood island, the early-mid yolk sac, and the late yolk sac-early fetal-liver hematopoietic programs within the mouse embryo.
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References
Doetschman, T. C., Eistetter, H., Katz, M., Schmidt, W., and Kemler, R. (1985) The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J. Embryol. Exp. Morphol. 87, 27–45.
Wiles, M. and Keller, G. (1991) Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development 111, 259–267.
Schmitt, R., Bruyns, E., and Snodgrass, H. (1991) Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. Genes Dev. 5, 728–740.
Burkert, U., von Ruden, T., and Wagner, E. F. (1991) Early fetal hematopoietic development from in vitro differentiated embryonic stem cells. New Biol. 3, 698–708.
Keller, G., Kennedy, M., Papayannopoulou, T., and Wiles, M. (1993) Hematopoi-etic commitment during embryonic stem cell differentiation in culture. Mol. Cell. Biol. 13, 473–486.
Nakano, T., Kodama, H., and Honjo, T. (1994) Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science 265, 1098–1101.
Keller, G. (1995) In vitro differentiation of embryonic stem cells. Curr. Opin. Cell Biol. 7, 862–869.
Kennedy, M., Firpo, M., Choi, K., Wall, C., Robertson, S., Kabrun, N., et al. (1997) A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386, 488–493.
Kabrun, N., Buhring, H. J., Choi, K., Ullrich, A., Risau, W., and Keller, G. (1997) Flk-1 expression defines a population of early embryonic hematopoietic precursors. Development 124, 2039–2048.
Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J. C., and Keller, G. (1998) A common precursor for hematopoietic and endothelial cells. Development 125, 725–732.
Nishikawa, S. I., Nishikawa, S., Hirashima, M., Matsuyoshi, N., and Kodama, H. (1998) Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin+ cells at a diverging point of endothelial and hemopoietic lineages. Development 125, 1747–1757.
Weiss, M., Keller, G., and Orkin, S. (1994) Novel insights into erythroid development revealed through in vitro differentiation of GATA-1- embryonic stem cells. Genes Devel. 8, 1184–1197.
Tsai, F. Y., Keller, G., Kuo, F. C., Weiss, M., Chen, J., Rosenblatt, M., et al. (1994) An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 371, 221–226.
Porcher, C., Swat, W., Rockwell, K., Fujiwara, Y., Alt, F. W., and Orkin, S. H. (1996) The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell 86, 47–57.
Epner, E., Reik, A., Cimbora, D., Telling, A., Bender, M. A., Fiering, S., et al. (1998) The beta-globin LCR is not necessary for an open chromatin structure or developmentally regulated transcription of the native mouse beta-globin locus. Molecular Cell 2, 447–455.
Helgason, C. D., Sauvageau, G., Lawrence, H. J., Largman, C., and Humphries, R. K. (1996) Overexpression of HOXB4 enhances the hematopoietic potential of embryonic stem cell differentiated in vitro. Blood 87, 2740–2749.
Keller, G., Wall, C., Fong, A., Hawley, T., and Hawley, R. (1998) Overexpression of HOX11 leads to the immortalization of embryonic precursors with both primitive and definitive hematopoietic potential. Blood 92, 877–887.
Karasuyama, H. and Melchers, F. (1988) Establishment of mouse cell lines which constitutively secrete large quantitites of interleukin 2, 3, 4, or 5 using modified cDNA expression vectors. Eur. J. Immunol. 18, 97–104.
Robertson, E. J., ed., (1987) Teratocarcinomas and embryonic stem cells: a practical approach. (D. Rickwood and B. Hames, eds. Hames.) IRL Press, Oxford, Washington, DC.
Williams, R. L., Hilton, D. J., Pease, S., Willson, T. A., Stewart, C. L., Gearing, D. P., Wagner, E. F., Metcalf, D., Nicola, N. A., and Gough, N. M. (1988) Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 336, 684–687.
Smith, A. G., Heath, J. K., Donaldson, D. D., Wong, G. G., Moreau, J., Stahl, M., et al. (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336, 688–690.
Newman, P. J. (1994) The role of PECAM-1 in vascular cell biology. Ann. NY Acad. Sci. 714, 165–174.
Millauer, B., Wizigmann-Voos, S., Schnurch, H., Martinez, R., Moller, N. P., Risau, W., et al. (1993) High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72, 835–846.
Yamaguchi, T. P., Dumont, D. J., Conlon, R. A., Breitman, M. L., and Rossant, J. (1993) flk-1, an flt-related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development 118, 489–498.
Fong, G. H., Klingensmith, J., Wood, C. R., Rossant, J., and Breitman, M. L. (1996) Regulation of flt-1 expression during mouse embryogenesis suggests a role in the establishment of vascular endothelium. Dev. Dyn. 207, 1–10.
Dumont, D. J., Yamaguchi, T. P., Conlon, R. A., Rossant, J., and Breitman, M. L. (1992) tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors. Oncogene 7, 1471–1480.
Russel, E. (1979) Heriditary anemias of the mouse: a review for geneticists. Adv. Genet. 2, 357–459.
Barker, J. (1968) Development of the mouse hematopoietic system I. Types of hemoglobin produced in embryonic yolk sac and liver. Dev. Biol. 18, 14–29.
Brotherton, T., Chui, D., Gauldie, J., Patterson, M. (1979) Hemoglobin ontogeny during normal mouse fetal development. Proc. Natl. Acad. Sci. USA 76, 2853–2857.
Hume, D. A., Robinson, A. P., Macpherson, G. G., and Gordon, S. (1983) The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. J. Exp. Med. 158, 1522–1536.
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© 2002 Humana Press Inc., Totowa, NJ
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Keller, G.M., Webb, S., Kennedy, M. (2002). Hematopoietic Development of ES Cells in Culture. In: Klug, C.A., Jordan, C.T. (eds) Hematopoietic Stem Cell Protocols. Methods in Molecular Medicine, vol 63. Humana Press. https://doi.org/10.1385/1-59259-140-X:209
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DOI: https://doi.org/10.1385/1-59259-140-X:209
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